title: Punicalagin, a polyphenol in pomegranate juice, downregulates p53 and attenuates hypoxia-induced apoptosis in cultured human placental syncytiotrophoblasts.
abstract: Oxidative stress is associated with placental dysfunction and suboptimal pregnancy outcomes. Therapeutic interventions to limit placental injury from oxidative stress are lacking. Punicalagin is an ellagitannin and a potent antioxidant in pomegranate juice. We showed that both pomegranate juice and punicalagin decrease oxidative stress and apoptosis in cultured syncytiotrophoblasts. p53 is involved in the oxidative stress-induced apoptosis in trophoblasts. We now test the hypothesis that punicalagin limits trophoblast injury in vitro by regulating the levels of p53. We examined the expression of p53, mouse double minute 2 homolog, p21, hypoxia-inducible factor (HIF) α, and selected members of the B cell lymphoma 2 (BCL2) family of proteins in cultured syncytiotrophoblasts exposed to ≤1% oxygen in the absence or presence of punicalagin. We found that punicalagin attenuated hypoxia-induced apoptosis in syncytiotrophoblasts, as quantified by levels of cleaved poly-ADP ribose polymerase. This protective effect was in part mediated by reduced p53 activity shown by decreased expression of p21, lower HIF1α expression, and limited activity of caspases 9 and 3. There was no change in expression of proteins in the BCL2 family, which are also important in apoptosis. The data support a role for downregulation of p53 in the protection of human trophoblasts by punicalagin.
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Baosheng
authors.initials: B
authors.lastname: Chen
authors.forename: Mark S
authors.initials: MS
authors.lastname: Longtine
authors.forename: D Michael
authors.initials: DM
authors.lastname: Nelson
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001628:Beverages; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D029561:Lythraceae / Q000737:chemistry*; D051379:Mice; D059808:Polyphenols / Q000494:pharmacology; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D047348:Hydrolyzable Tannins; D059808:Polyphenols; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C115642:punicalagin
keywords: hypoxia-inducible factor α; mouse double minute 2 homolog; placenta